dMIL-Transformer: Multiple Instance Learning Via Integrating Morphological and Spatial Information for Lymph Node Metastasis Classification

Abstract

Automated classification of lymph node metastasis (LNM) plays an important role in the diagnosis and prognosis. However, it is very challenging to achieve satisfactory performance in LNM classification, because both the morphology and spatial distribution of tumor regions should be taken into account. To address this problem, this article proposes a two-stage dMIL-Transformer framework, which integrates both the morphological and spatial information of the tumor regions based on the theory of multiple instance learning (MIL). In the first stage, a double Max-Min MIL (dMIL) strategy is devised to select the suspected top-K positive instances from each input histopathology image, which contains tens of thousands of patches (primarily negative). The dMIL strategy enables a better decision boundary for selecting the critical instances compared with other methods. In the second stage, a Transformer-based MIL aggregator is designed to integrate all the morphological and spatial information of the selected instances from the first stage. The self-attention mechanism is further employed to characterize the correlation between different instances and learn the bag-level representation for predicting the LNM category. The proposed dMIL-Transformer can effectively deal with the thorny classification in LNM with great visualization and interpretability. We conduct various experiments over three LNM datasets, and achieve 1.79%-7.50% performance improvement compared with other state-of-the-art methods.